Precatalyst‐Enabled Selectivity: Enantioselective NiH‐Catalyzed anti‐Hydrometalative Cyclization of Alkynones to Endo‐ and Heterocyclic Allylic Alcohols

Abstract

A highly enantioselective NiH‐catalyzed hydrocyclization of alkynones with unparalleled anti‐ and endocyclic selectivities is described. The choice of the precatalysts has significant influence in tuning the regio‐ and enantioselectivity. Using Ni(OTs)2/Phox as a precatalyst and (EtO)2MeSiH as a hydride source, an array of enantioenriched O‐, N‐, and S‐containing heterocyclic tertiary allylic alcohols are obtained in 24–81 % yields with 80:20–99:1 er. Mechanistic investigations and synthetic application are also carried out. This study represents an efficient access to a set of allylic alcohols that are unable to access by the state‐of‐the‐art coupling reactions.

Nickel-catalyzed cyanation reaction of aryl/alkenyl halides with alkyl isocyanides

“…Both E - and Z -(2-iodovinyl)benzenes proved to be viable substrates and reaction of Z -(2-iodovinyl)benzene with 2a gave the E cinnamonitrile, presumably due to alkenylnickel isomerization. 13 Finally, we conducted a reaction of 4-iodobenzaldehyde 1m with 2a on a scale of 5 mmol. To our delight, the desired product 3m was isolated in 51% yield ( 3m , Scheme 2, in the parentheses).…”

Recent developments in nickel-catalyzed asymmetric cyclization and cycloaddition of carbonyl-alkynes, cyano-alkynes, and enynes

“…In 2021, Liu and co-workers developed a novel strategy for the NiH-catalyzed anti -hydrometalative cyclization of carbonyl-alkynes with (EtO) 2 MeSiH in the presence of Ni(OTs) 2 ·6H 2 O (8 mol%) and InPhox L8 (12 mol%) in toluene at 90 °C (Scheme 15). 33 Substrates with a range of substituents on the alkyne or ketone moiety including electron-donating or electron-withdrawing aromatics ( 44a ), heteroaryl ( 44b and 44c ), and alkyl ( 44d and 44e ) groups were tolerated in the reaction. It is notable that alkyl-substituted carbonyl-alkynes showed an inferior regioselectivity in the cyclization reaction ( 44e and 44e′ ).…”

Endo-Selective Intramolecular Alkyne Hydroamidation Enabled by NiH Catalysis Incorporating Alkenylnickel Isomerization

“…To this end, we conceived an alternative inner-sphere − approach based on NiH catalysis, − which would allow us to define the bond-forming carbon site prior to the cyclization, in a highly predictable manner (Scheme c). With hydronickelation known to take place commonly by syn addition, one imperative requisite for this reaction design would be the ability to incorporate alkenylnickel E / Z isomerization. − This unique mechanistic handle has in fact been broadly utilized for C–C bond-forming cyclization, − but scarcely for the C–N equivalents. Although a few examples have been reported for intramolecular arylative amination of alkynes with azides, these reactions are specific to highly activated structures that are prone to further aromatization to rather give unsaturated heteroarenes. , Thus, the development of new alkenylnickel isomerization strategy for delicately controlled endo -selective amidative cyclization would be extremely appealing.…”